The emerging role of KDM5A in human cancer

Abstract

Histone methylation is a key posttranslational modification of chromatin, and its dysregulation affects a wide array of nuclear activities including the maintenance of genome integrity, transcriptional regulation, and epigenetic inheritance. Variations in the pattern of histone methylation influence both physiological and pathological events. Lysine-specific demethylase 5A (KDM5A, also known as JARID1A or RBP2) is a KDM5 Jumonji histone demethylase subfamily member that erases di- and tri-methyl groups from lysine 4 of histone H3. Emerging studies indicate that KDM5A is responsible for driving multiple human diseases, particularly cancers. In this review, we summarize the roles of KDM5A in human cancers, survey the field of KDM5A inhibitors including their anticancer activity and modes of action, and the current challenges and potential opportunities of this field.

Towards the simulation of large scale protein–ligand interactions on NISQ-era quantum computers

“…5(a) . KDM5A is believed to be relevant for human cancers 23 and contains a metal center [Fe( ii )] which may pose a challenge for classical electronic structure theory methods. To make the problem tractable, we used a model system of the binding site which was cut out from the full binding domain of KDM5A and focuses on the immediate surrounding of metal ion and ligand.…”

“…Next we discuss the VQE ansatz used in this work, although the SAPT method itself is largely independent of the way in which the ground state properties are computed. Finally we benchmark our method using ideal quantum simulators and demonstrate a significant reduction in error found when poorly converged VQE wavefunctions are used for model multi-reference systems and for the human cancer relevant 23 lysine-specific demethylase 5 (KDM5A) protein with different ligand substitutions.…”

Emerging roles for lncRNA-NEAT1 in colorectal cancer

“…NEAT1 silencing repressed the malignant features of CRC cells [ 79 ]. Lysine-specific demethylase 5A (KDM5A) which is participated in human cancer has been inhibited through binding of NEAT1 to the E2F transcription factor 1 (E2F1) protein [ 79 , 80 ]. E2F1 is known to be associated with the pathogenesis, metastasis, and chemoresistance of CRC cells [ 81 ].…”

HIF-1-Independent Mechanisms Regulating Metabolic Adaptation in Hypoxic Cancer Cells

“…These rapid histone hypermethylations occurred independently of HIF-1 and of other known hypoxia-inducible inhibitors of KDM activity, such as reactive oxygen species and 2-hydroxyglutarate [ 110 , 111 ]. Overexpressed in several different types of human cancers [ 112 ], KDM5A has been reported to control differentiation and mitochondrial metabolism by directly repressing metabolic regulatory genes. Loss of the KDM5A gene in pRb-deficient murine embryonic fibroblasts restored differentiation by increasing mitochondrial respiration [ 113 ].…”